1. Field of the Invention
The present invention generally relates to apparatus and methods for treatment of eating disorders, such as obesity, bulimia nervosa, and anorexia nervosa, and more particularly to treatments and therapies which employ vagus nerve stimulation in the esophageal/gastric area of the body in conjunction with gastric restriction.
2. Description of Related Art
Increasing prevalence of obesity is one of the most serious and widespread health problems in the world. It is estimated that about 6% of the current population of the United States is morbidly obese, defined as having a body mass index of more than forty, or as is more commonly understood, being more than one hundred pounds overweight for a person of average height. In addition to the morbidly obese, a much larger percentage of the population is either obese or significantly overweight. Aside from what may be an epidemic of obesity, it is believed by some health experts that obesity is one of the first two leading causes of preventable deaths in the United States, either ahead of or just behind cigarette smoking.
The classical treatment regimen for obese persons, which combines nutritional counseling with exercise and education, has demonstrated relatively little long term success. In general, liquid diets and pharmaceutical agents can bring about acute, but rarely lasting, weight loss. Surgery to provide either gastric restriction or malabsorption in cases of severe obesity have shown the greatest success long-term, but are major surgical procedures that can lead to emotional problems, and which have their share of failures (see, e.g., Kriwanek, “Therapeutic failures after gastric bypass operations for morbid obesity,” Langenbecks Archiv. Fur Chirurgie, 38(2): 70-74, 1995).
Among the surgical approaches to the treatment of morbid obesity, various stomach banding or gastroplasty ring devices have been employed for gastric restriction (i.e., decreasing the size of the stomach) to reduce food intake. For example, U.S. Pat. No. 4,592,339 (Mentor Corporation), U.S. Pat. Nos. 5,074,868, 5,226,429 and 5,601,604 (Inamed Development Co.), and U.S. Pat. Nos. 5,771,903 and 6,102,922 (Kirk Promotions Limited). Some of the known gastric bands have incorporated an inflatable member for adjusting the diameter of the stoma opening created by the band.
There have also been efforts to treat obesity, and syndromes related to motor disorders of the stomach of a patient, by altering natural gastric motility of the patient. For example, U.S. Pat. No. 5,423,872 (Cigaina) identifies a “gastric pacemaker” region of the stomach, at a point proximate to the greater curvature, at which propulsive gastric movements begin and from which electrical pulses (depolarization potential) spread in an anterograde direction along the entire stomach. The patent describes a process of altering, by means of sequential electrical pulses and for preset periods of time, the natural gastric motility of a patient and/or the time and manner of contraction of the lower esophageal and pyloric sphincters to prevent emptying (or to slow down) gastric transit, to prevent duodenal acidification during interdigestive phases, or to prevent gastric reflux in the last portion of the esophagus. The stimulator device is placed subcutaneously in the abdominal wall and is connected to the distal gastric antrum by means of an electrocatheter.
U.S. Pat. No. 5,690,691 (The Center for Innovative Technology) describes an implantable or portable gastrointestional pacemaker for any organ in the gastro-intestinal tract through which peristaltic movement of material is controlled by natural electrical pacing, and includes multiple electrodes that are positionable at multiple sites on a single organ or on different sites on different organs. Feedback from the gastrointestinal tract can be provided by one or more sensor electrodes.
U.S. Pat. App. Pub. No. 2003/0208212 (Cigaina) describes a removable gastric band which may be paired with the use of a gastric electrostimulator for inducing forced slimming in the initial phase of treatment for morbigenous obesity. Such electrostimulation devices may either be incorporated into the removable gastric band or located at a distance from the removable gastric band.
U.S. Pat. No. 6,510,332 (Transneuronix, Inc.) describes an implant device for electrostimulation and/or electrical monitoring of endo-abdominal tissue or viscera. In the background discussion of that patent it is said that stimulation of the intrinsic nervous system of the stomach is likely to have two major consequences or effects: (1) the correction and direct control of the electromotor activity of the intestines and (2) the stimulation of increased incretion of specific substances (i.e., gastroenteric neuromediators) produced by the intrinsic nervous system itself thorough the myenteric plexus.
In addition to electrical stimulation of gastrointestinal structures, treatment of eating disorders by stimulation of one or more cranial nerves, particularly the vagus nerve, is also known. U.S. Pat. No. 5,188,104 (Cyberonics, Inc.) describes methods and devices for stimulation of the vagus nerve to treat compulsive overeating and obesity, and other eating disorders such as bulimia and anorexia nervosa. In some procedures for treating obesity, the stimulating electrode is implanted about the vagus nerve or branch thereof in the esophageal region slightly above the stomach. Passage of food can be monitored via sensing electrodes as the patient swallows, and modulation of vagal activity may be initiated when a predetermined total amount of food has been consumed, when the patient perceives a need for treatment, according to circadian rhythms of the patient, or according to a schedule of preset time intervals.
U.S. Pat. No. 5,263,480 (Cyberonics, Inc.) describes treatment of obesity and compulsive overeating disorder by selectively applying modulating electrical signals to the patient's vagus nerve, preferably using an implanted neurostimulator. Modulating signals may be used to stimulate vagal activity to increase the flow of neural impulses up the nerve (i.e., afferent action potentials), or to inhibit vagal activity to block neural impulses from moving up the nerve, thereby producing excitatory or inhibitory neurotransmitter release. Both ways of modulating vagus nerve electrical activity have been termed vagus nerve stimulation (VNS).
The '480 patent describes the use of VNS for appetite suppression by causing the patient to experience satiety, which would result in decreased food consumption and consequent weight reduction. A pulse generator is implanted in a convenient location in the patient's body, attached to an electrical lead having a nerve electrode coupled to the vagus nerve (or a branch thereof) in the esophageal region slightly above the stomach. The pulse generator is triggered to apply VNS therapy and thereby reduce or eliminate the patient's appetite. VNS therapy may be applied periodically or intermittently during the patient's normal waking hours according to a preset duty cycle, such as thirty seconds on-time and five minutes off-time. In alternate embodiments, electrical stimulation may be provided as a continuous pulse train throughout the day except at mealtimes, and the patient may manually activate the stimulus generator by a variety of known methods such as placing an external magnet on the skin overlying the implanted stimulus generator, or by tapping the stimulus generator through the skin in the same area. See, e.g., U.S. Pat. No. 5,304,206. VNS may also be initiated if the patient's food consumption over a given period exceeds a predetermined threshold level, detected and measured for example by sensing electrodes implanted at or near the esophagus. Patient intervention assumes a patient with an earnest desire to control his or her eating behavior, but normally lacking sufficient willpower to control the compulsive behavior without the support of VNS therapy.
More recently, U.S. Pat. App. Pub. No. 2004/0167581 (Knudson et al.) describes a gastric band with electrodes for vagus nerve stimulation. This application is directed to treatment of functional dyspepsia, irritable bowel syndrome, gastroparesis, gastroesophageal reflux disease (GERD), by blocking intrinsic (i.e., natural) vagus nerve action potentials traveling along the nerve. To the extent that the '581 application is concerned with treating eating disorders, it is specifically intended to block native action potentials from traveling along the nerve, as opposed to inducing artificial afferent or efferent action potentials. See '581 application at paragraphs 150-155. Although blocking of certain native action potentials (i.e., at certain time periods) may be included within the scope of the present invention, in contrast to the aforementioned '581 application the present invention in preferred embodiments includes the generation of induced afferent and/or efferent action potentials on the vagus nerve, with or without blocking of native action potentials.
Notwithstanding the foregoing prior art, there remains a need for improved therapies and devices to provide gastric restriction and/or vagus nerve stimulation for treatment of eating disorders. Accordingly, it is an object of the present invention to provide improved methods and devices for combining gastric restriction with vagus nerve stimulation for the treatment of eating disorders. It is a further object of the present invention to provide improved methods and devices for the treatment of eating disorders by combining gastric restriction with vagus nerve stimulation for inducing afferent and/or efferent action potentials on the vagus nerve. It is a still further object of the invention to provide a gastric band for the treatment of eating disorders that may be adjusted after implantation into the patient's body. It is an additional object of the present invention to provide a gastric band that may be post-operatively and noninvasively adjusted by a physician using an external adjustment device after implantation of the band. It is another object of the present invention to provide a gastric band capable of both sensing and stimulating the vagus nerve. It is yet another object of the invention to provide improved methods and devices to minimize electrical energy usage in providing electrical stimulation of the vagus nerve for the treatment of eating disorders. It is another object of the present invention to use induced action potentials on the vagus nerve to determine which electrodes among a plurality of electrodes on a gastric band have the most effective electrical communication with the vagus nerve.
The Vagus Nerve
The vagus nerve, the tenth cranial nerve, originates from the brain stem, passing through foramina of the skull to parts of the head, neck and trunk. It is a mixed nerve, with both sensory and motor fibers, the sensory fibers being primary and attached to neuron cell bodies located outside the brain in ganglia groups, and the motor fibers attached to neuron cell bodies located within the gray matter of the brain. Somatic fibers of the cranial nerves are involved in conscious activities and connect the CNS (central nervous system) to the skin and skeletal muscles, while autonomic fibers of these nerves are involved in unconscious activities and connect the CNS to the visceral organs such as the heart, lungs, stomach, liver, pancreas, spleen, and intestines.
Motor fibers of the vagus nerve transmit impulses from the brain to the muscles associated with speech and swallowing, the heart, and smooth muscles of the visceral organs of the thorax and abdomen. In contrast, the vagus nerve's sensory fibers transmit impulses from the pharynx, larynx, esophagus and visceral organs of the thorax and abdomen to the brain. At the base of the brain, the vagus nerve branches into the left and right vagi, which run respectively through the left and right sides of the neck and trunk.
The vagus nerve, including both the right and left branches or vagi, is the dominant nerve enervating the gastrointestinal (GI) tract. After branching from the spinal cord, the vagal afferents transport information regarding the GI tract to the brain. In the lower part of the chest, the left vagus rotates anteriorly to become the anterior vagus, which innervates the stomach by branches distributed over its anterosuperior surface. Some of those branches extend over the fundus and others along the lesser curvature of the stomach, as illustrated in simplified form in FIG. 2. The right vagus rotates to become the posterior vagus (not shown in FIG. 2), where it is distributed to the postero-inferior surface of the stomach, forming the celiac division, joining the left side of the celiac plexus, and innervating the duodenum and proximal intestinal tract.
While the vagus is often considered to be a motor nerve that also carries sensory signals, 80% of the individual nerve fibers are sensory afferent fibers (e.g., Grundy et al., “Sensory afferents from the gastrointestinal tract,” Chapter 10, HANDBOOK OF PHYSIOLOGY, Sec. 6, S.G., Ed., American Physiology Society, Bethesda, Md., 1989). Afferent nerve impulses are conducted inwardly toward a nerve center, such as the brain or spinal cord, via afferent nerve fibers. Efferent nerve impulses are conducted outwardly or away from a nerve center along efferent nerve fibers, usually going to an effector to stimulate it and produce activity. Thus, for purposes of the present application, vagal afferent signals transmit sensory information to the brain from the gastrointestinal tract, and vagal efferent signals transmit motor signals from the brain to the GI tract.
The exact mechanisms leading an individual to experience a feeling of satiety or appetite reduction are not fully known, but a substantial amount of information has been accumulated and reported in the literature. Satiety signals include the stretch of mechanoreceptors and the stimulation of certain chemosensors (“A Protective Role for Vagal Afferents: An Hypothesis,” NEUROANATOMY AND PHYSIOLOGY OF ABDOMINAL VAGAL AFFERENTS, Chapter 12, CRC Press, New York, N.Y., 1992). These signals are transported to the brain by the nervous system or endocrine factors such as gut peptides (“External Sensory Events and the Control of the Gastrointestinal Tract: An Introduction,” id. at Chapter 5). It has been demonstrated that direct infusion of maltose and oleic acid into the duodenum of rats leads to a reduction in food intake, and that this reduced food consumption response is ablated by vagotomy or injection of capsaicin, which destroys vagal afferents. Introduction of systemic cholecystokinin also reduces food intake in rats, and is likewise ablated by destruction of vagal afferents. An accepted and well-researched hypothesis is that some vagal sensory information is used to control food intake. Experiments have shown that the gastrointestinal (GI) tract is the most likely source of signals contributing to the termination of eating (see, e.g., Neuroanatomy and Physiology of Abdominal Vagal Afferents, Ch. 10 Ritter, Ritter and Barnes, Ed., CRC Press, 1992 The predominant view is that, from the gastrointestinal tract, cholecystokinin and other peptides are released after a meal to coordinate several aspects of digestion, absorption, and metabolism and to transmit information to the brain, via the vagus nerve, that signals meal termination and satiety (see Leibowitz, Eating Disorders and Obesity, A Comprehensive Handbook, Ch. 1, Brownell and Fairbum, Ed., The Guilford Press, 1995). The left and right vagi, or anterior and posterior as they are called in the thoracic and GI area, selectively innervate various areas of the viscera such as the stomach and intestines. Stimulation of both vagi would insure that afferent (towards the brain) signals from all visceral organs are created.
U.S. Pat. No. 6,587,719 (Cyberonics, Inc.) describes a method of treating patients for obesity by bilateral stimulation of the patient's vagus nerve (i.e., bilateral VNS). A stimulating electrical signal, with parameters determined to induce weight loss, is applied to one or both branches of the vagus. The signal is preferably a pulsed signal applied according to a set duty cycle (i.e., on and off times) intermittently to both vagi. In any event, VNS is applied at a supra-diaphragmatic position (i.e., above the diaphragm) in the ventral cavity. The electrical pulse stimuli are set at a current magnitude below the retching level of the patient (e.g., not exceeding about 6 milliamperes (mA), to avoid patient nausea) in alternating periods of continuous application (via a train or series of electrical pulses) and no application. Pulse width is set at or below 500 microseconds (μs), and pulse repetition frequency at about 20-30 Hz. The on/off duty cycle (i.e., first period/second period of the alternating periods) is programmed to a ratio of about 1:1.8. The neurostimulator, which may be a single device or a pair of devices, is implanted and electrically coupled to lead(s) having nerve electrodes implanted on the right and left branches of the vagus.
U.S. Pat. No. 6,609,025 (Cyberonics, Inc.) describes a similar method of treating patients for obesity by unilateral or bilateral stimulation of either or both of the left and right vagi; however the electrical stimulation is applied at a sub-diaphragmatic position (i.e., below the diaphragm). It is theorized that sub-diaphragmatic stimulation may provide an enhanced effect in inducing a feeling of satiety because it is administered in closer proximity to the stomach itself.